The AIDS epidemic has served as a catalyst for experimentation in the organization of inpatient care which, if carefully evaluated, could yield promising solutions to many of the persistent problems of hospitals including a dissatisfied and unstable nurse work force and uneven quality of care. Two models for organizing inpatient care have emerged as hospitals in high HIV incidence cities have responded to the AIDS epidemic: dedicated AIDS units with contiguous beds and a separate nursing staff specializing in the care of people with HIV-related illnesses, and scattered-beds located usually on multidiagnosis medical units. Debate on the pros and cons of these two models has been heated but empirical evidence has been largely lacking. Proposed is a 23 hospital study comparing clinical and economic outcomes of care provided in these two models. The study is a comparative, multi-site observational study, in which matching is employed at the hospital level to introduce the control elements of quasi-experimental design. Approximately 1650 patients will be studied, half having received their care in dedicated AIDS units and half in scattered-beds on medical units. Using state-of-the-science instruments to stage severity of illness, the study will examine inhospital mortality, patient satisfaction, length of stay, destination at discharge, and costs. GRANT=R01HL47569 The long-range objective of this project is to determine the role of interleukin 1 (IL1) and the related cytokines, interleukin 6 (IL6), tumor necrosis factor (TNF), and interferon-gamma (IFN-gamma) in the physiological and pathophysiological modulation of vascular tone, The proposed research will test the hypothesis that autocrine or paracrine actions of IL1 and/or IL6 produced within blood vessels modulate systemic vascular resistance and local blood flow in vivo. These studies will: (1) Determine whether IL6, TNF, or IFN-gamma act independently or synergistically with IL1 to induce nitric oxide (NO) production in cultured human vascular smooth muscle cells (VSMC). (2) Determine whether cytokines, including IL6, TNF, and/or IL1, are produced by VSMC and mediate the known activation of NO synthase in VSMC by bacterial endotoxin. This will be achieved by analysis of released cytokines using enzyme-linked immunosorbent assays (ELISA), and by immunoneutralization of cytokines using specific antibodies. (3) Determine which vascular cell types and which vascular beds produce IL1 and IL6 in vivo, in both normal and LPS-treated rats, using in situ hybridization to detect IL1 and IL6 mRNA and immunocytochemistry to detect IL1 and IL6. (4) Determine whether second messengers or vasoactive agonists regulate IL1 or IL6 production and/or release by cultured human VSMC, using Northern analysis to measure IL1 and IL6 mRNA levels and ELISA techniques to measure IL1 and IL6. (5) Whether IL1 induces endothelin gene expression in human VSMC in vitro. The proposal is based on my recent demonstration that IL1, a monocyte- and macrophage-derived cytokine, is a vasodilator which acts directly on vascular smooth muscle. In contrast to the rapid and transient actions of endothelium-dependent vasodilators, the effect of IL1 is slow in onset and prolonged, lasting hours to days. Preliminary studies further indicate that IL1 and IL6 are produced by vascular tissue in vivo. Therefore, autocrine actions of IL1 and IL6 produced within VSMC may play a significant role in long-term modulation of vascular tone. Furthermore, cytokines produced by either immune cells or vascular cells probably contribute to the vasodilatation associated with local inflammation, hemodialysis therapy, and septic shock, a major cause of human mortality. Understanding the roles of cytokines in modulating vascular tone may improve our ability to control these significant complications of human disease.